Synthesis of a Pentasaccharide and Neoglycoconjugates Related to Fungal α-(1→3)-Glucan and Their Use in the Generation of Antibodies to Trace Aspergillus fumigatus Cell Wall

• Published in: Chemistry : a European journal 2015-01, Vol.21 (3), p.1029-1035
• Main Authors: Komarova, Bozhena S., Orekhova, Maria V., Tsvetkov, Yury E., Beau, Remi, Aimanianda, Vishukumar, Latgé, Jean-Paul, Nifantiev, Nikolay E.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibodies - immunology; Aspergillus; Aspergillus fumigatus; Aspergillus fumigatus - metabolism; Bearing; Biotin; Biotin - chemistry; Biotin - immunology; carbohydrates; Cattle; Cell Wall; Cell Wall - metabolism; Chemical Sciences; Conjugates; Female; Glucans; Glucans - chemistry; Glucans - immunology; Glucans - metabolism; Glycoconjugates; Glycoconjugates - chemical synthesis; Glycoconjugates - chemistry; Glycoconjugates - immunology; glycosylation; imaging agents; Joining; Life Sciences; Mice; Mice, Inbred BALB C; Microbiology and Parasitology; Mycology; Oligosaccharides; Oligosaccharides - chemical synthesis; Oligosaccharides - chemistry; Oligosaccharides - immunology; Organic chemistry; protecting groups; Serum Albumin, Bovine; Serum Albumin, Bovine - chemistry; Serum Albumin, Bovine - immunology; Synthesis; Walls
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201404770

3‐Aminopropyl α‐(1→3)‐pentaglucoside, a fragment of α‐(1→3)‐glucan of the cell wall of Aspergillus fumigatus, has been synthesized in a blockwise approach. The application of mono‐ and disaccharide N‐phenyltrifluoroacetimidates bearing a stereodirecting 6‐O‐benzoyl group was essential for stereoselective α‐glucosylations. In the products, p‐methoxyphenyl and levulinoyl groups served as orthogonal protecting groups for the anomeric position and 3‐OH group, respectively. Their removal from shared blocks led to donors and acceptors that were used for the synthesis of pentasaccharides. Coupling of free α‐(1→3)‐pentaglucoside with biotin and bovine serum albumin (BSA) gave glycoconjugate tools for mycological studies. Immunization of mice with the BSA conjugate induced the generation of antibodies that recognize α‐(1→3)‐glucan on A. fumigatus cell wall and distinguish its morphotypes. This discovery represents a first step to the development of a diagnostic test system and a vaccine to detect and fight this life‐threatening pathogen. Directed disaccharides: Adhering to a concept of remote anchimeric assistance, a disaccharide block bearing a stereodirecting benzoyl group at O‐6 was constructed. A combination of orthogonal levulinic and methoxyphenyl protecting groups in shared blocks ensured straightforward chain extension. A couple of α‐selective glycosylations lead to spaced α‐pentasaccharide. The α‐(1→3)‐glucan conjugates derived from the pentasaccharide allowed specific anti‐α‐(1→3)‐glucan serum to be obtained for further immunolabeling of Aspergillus fumigatus cell wall.